The tetraspanin CD9 controls migration and proliferation of parietal epithelial cells and glomerular disease progression

Hélène Lazareth, Carole Henique (), Olivia Lenoir, Victor G. Puelles, Martin Flamant, Guillaume Bollée, Cécile Fligny, Marine Camus, Lea Guyonnet, Corinne Millien, François Gaillard, Anna Chipont, Blaise Robin, Sylvie Fabrega, Neeraj Dhaun, Eric Camerer, Oliver Kretz, Florian Grahammer, Fabian Braun, Tobias B. Huber, Dominique Nochy, Chantal Mandet, Patrick Bruneval, Laurent Mesnard, Eric Thervet, Alexandre Karras, François Naour, Eric Rubinstein, Claude Boucheix, Antigoni Alexandrou, Marcus J. Moeller, Cédric Bouzigues and Pierre-Louis Tharaux ()
Additional contact information
Hélène Lazareth: Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
Carole Henique: Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
Olivia Lenoir: Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
Victor G. Puelles: University Hospital RWTH Aachen
Martin Flamant: Xavier Bichat University Hospital, Université de Paris
Guillaume Bollée: Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
Cécile Fligny: Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
Marine Camus: Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
Lea Guyonnet: Luxembourg Institute of Health
Corinne Millien: Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
François Gaillard: Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
Anna Chipont: Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
Blaise Robin: Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
Sylvie Fabrega: Université de Paris, Institut Imagine, Plateforme Vecteurs Viraux et Transfert de Gènes, IFR94, Hôpital Necker Enfants-Malades
Neeraj Dhaun: Royal Infirmary of Edinburgh
Eric Camerer: Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
Oliver Kretz: University Medical Center Hamburg-Eppendorf
Florian Grahammer: University Medical Center Hamburg-Eppendorf
Fabian Braun: University Medical Center Hamburg-Eppendorf
Tobias B. Huber: University Medical Center Hamburg-Eppendorf
Dominique Nochy: Assistance Publique-Hôpitaux de Paris
Chantal Mandet: Assistance Publique-Hôpitaux de Paris
Patrick Bruneval: Assistance Publique-Hôpitaux de Paris
Laurent Mesnard: Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche S1155, Pierre and Marie Curie University
Eric Thervet: Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
Alexandre Karras: Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC
François Naour: Inserm U1193, Université Paris-Sud
Eric Rubinstein: Inserm U935, Université Paris-Sud
Claude Boucheix: Inserm U935, Université Paris-Sud
Antigoni Alexandrou: Ecole polytechnique, CNRS UMR7645, INSERM U1182, Université Paris-Saclay
Marcus J. Moeller: University Hospital RWTH Aachen
Cédric Bouzigues: Ecole polytechnique, CNRS UMR7645, INSERM U1182, Université Paris-Saclay
Pierre-Louis Tharaux: Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Center – PARCC

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: Abstract The mechanisms driving the development of extracapillary lesions in focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CGN) remain poorly understood. A key question is how parietal epithelial cells (PECs) invade glomerular capillaries, thereby promoting injury and kidney failure. Here we show that expression of the tetraspanin CD9 increases markedly in PECs in mouse models of CGN and FSGS, and in kidneys from individuals diagnosed with these diseases. Cd9 gene targeting in PECs prevents glomerular damage in CGN and FSGS mouse models. Mechanistically, CD9 deficiency prevents the oriented migration of PECs into the glomerular tuft and their acquisition of CD44 and β1 integrin expression. These findings highlight a critical role for de novo expression of CD9 as a common pathogenic switch driving the PEC phenotype in CGN and FSGS, while offering a potential therapeutic avenue to treat these conditions.

Date: 2019
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DOI: 10.1038/s41467-019-11013-2

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